Resonant sensor systems are microelectromechanical systems (“MEMS”) that can be used to measure the physical characteristics of a substance by detecting changes in resonant frequencies. Typically, resonant sensors utilize the ability of membranes to undergo physical deformation in response to external forces which cause vibrations or rhythmic motion. The membrane deformations are characterized by frequencies that are altered by the fluid medium surrounding the membrane, or by substances binding to the membrane that change the membrane's mass. By detecting frequencies in particular media or under particular conditions, resonant sensors are capable of generating signals that correspond to media or conditions (e.g., number or type of molecules in a solution) encountered by the resonant sensor.
In general, resonant sensor devices are capable of highly sensitive detection of changes in the physical characteristics of a fluid in contact with the sensor. However, resonant sensors are also highly sensitive to the presence of gas in a fluid, even if the gas is located relatively distant from the resonant surface of the resonant sensor device, because gases are compressible and, therefore, reduce the bulk fluid resistance to oscillations of the sensor surface. In most instances, gas is present in a sample or control fluid, or is trapped in areas of a fluid chamber where incomplete wetting of the surface occurs when fluid is introduced to the fluid chamber. Gas also can be formed in a sensor system as a vapor produced from heating a fluid, or by reducing the pressure of a fluid sample until the fluid transitions from a fluid state to a gas state. Furthermore, gas can nucleate to form bubbles or microbubbles (i.e., dimensions ≦400 μm) anywhere in the system, including locations upstream of the fluid chamber (e.g., sample or control fluid reservoirs, inlet connectors, inlet valves, and inlet ports) or on surfaces within the fluid chamber, including the surface of the resonant sensor device.
Bubbles or undissolved gas present significant limitations on the detection sensitivity achieved with resonant sensor devices. For example, stable measurements have not been maintained for periods of time longer than a few minutes due to gas in resonant sensor systems (see, e.g., Pyun et al., (1998) Biosensors & Bioelec. 13: 839-845). The short durations of time provided by previous techniques did not allow for significant data to be obtained during an experiment. Moreover, signals were stable over frequency ranges of between fifty and several hundred Hz/MHz (see, e.g., Cowan et al., (1999) Anal. Chem. 71:3622-3626). Such detection instability has prevented the identification of small or moderate changes in the characteristics of a solution. Furthermore, small or medium-sized molecules in a fluid could not be detected but, rather, only the largest biomolecules could be detected by these systems.
A need therefore exists for systems and methods that reduce the effect of gas on the performance of resonant sensor systems.